Infection, BacterialPhase 4MAX-AMOXNCT04070469
Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment (MAX-AMOX)
A Phase 4 study testing Amoxicillin in people with Infection, Bacterial, run by University Hospital, Clermont-Ferrand at 1 site in France.
Trial summary
Amoxicillin is the most prescribed antibiotic in France. High dose intravenous amoxicillin, (dosage greater than or equal to 150 mg / kg / day or 12 g per day for patients over 80 kg) is used in the treatment, in particular, of infectious streptococcal endocarditis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Bacterial
- What is being tested?
- Amoxicillin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 1 siteFrance
- Study dates
- 4 Dec 2019to 19 Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Major patient, male or female, who has a bacterial infection requiring high dose intravenous amoxicillin antibiotic therapy (greater than or equal to 150 mg / kg / day with a maximum of 12 grams per day or 12 grams per day for patients over 80 kg), according to ANSM recommendations.
- Able to provide informed consent to participate.
- Covered by a Social Security scheme.
Who cannot join
- Pregnant, breastfeeding, or likely to be pregnant women and in the absence of a negative pregnancy test (blood HCG beta).
- Patients under guardianship, curatorship, deprived of liberties or subject to a safeguard of justice.
- Septic shock justifying treatment with pressurized amines.
- Patient under ventilatory or circulatory support.
- Patients on dialysis at Baseline or with a creatinin clearance less than or equal to 30mL / min
- Refusal of participation
- Hypersensitivity to the active substance, to penicillins. History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam (e.g. cephalosporin, carbapenem or monobactam)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment : Intra- and Inter-individual Variability, Factors Associated With Overdose and Adverse Events
Amoxicillin is the most prescribed antibiotic in France. High dose intravenous amoxicillin, (dosage greater than or equal to 150 mg / kg / day or 12 g per day for patients over 80 kg) is used in the treatment, in particular, of infectious streptococcal endocarditis. oral, streptococci gallolyticus and enterococci, infections of the central nervous system with sensitive germs including Streptococcus pneumoniae and Listeria monocytogenes, osteo articular infections. The dose-related adverse effects of this antibiotic are nephrological (crystalluria may lead to acute renal failure) and neurologic. Recently, the number of amoxicillin crystalluria reported to pharmacovigilance centers has increased, having led the National Agency of drug and health products safety (ANSM) to recommend the determination of the residual level of amoxicillin during the first week of treatment of these patients. Nevertheless, there is no precise therapeutic target in patients treated with high dose amoxicillin except in the context of critical care. The authors suggest the interest of a target between 4 and 10 times the minimum inhibitory concentration (MIC) based on in vitro efficacy studies, and retrospective observations of toxicity cases.
Read the detailed description
Patients will be followed for 8 days. After inclusion, (day of the introduction of high-dose amoxicillin treatment), the residual amoxicillin plasma concentrations will be determined at Day1, Day4 +/- 1 day and Day7 +/- 1 day of the start of treatment. A urine collection will be performed the same day to search for crystalluria and measure the pH and urinary density.
In case of KDIGO (Kidney Disease Improving Global Outcomes) 2 or 3 stage renal failure or neurological signs compatible with overdose, residual amoxicillin and crystalluria and urinary density and urinary pH will be measured during the day of discovery of renal failure.
In the case of KDIGO stage 1 kidney failure, a residual level of amoxicillin and a crystalluria search and the measurement of urinary density and urinary pH will be carried out the following day, when serum creatinine is checked according to usual practices.
At day 7 the clinical and infectious biological evolution of the patient will be collected.
- Conditions
- Infection, Bacterial
- Being tested
- Amoxicillin
- Keywords
- amoxycillin, drug kinetics, drug toxicity, crystalluria
- Medical subject headings
- Bacterial Infections, Drug-Related Side Effects and Adverse Reactions, Crystalluria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmoxicillinDrug
Also called amoxicillin treatment
dosage of plasma concentration of amoxicillin
| Study group | Role | What they receive |
|---|---|---|
| Patient reveiving amoxycillin | Experimental | all patient included in this study Receives: Drug: Amoxicillin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Residual plasma concentrations of administered in high doses amoxicillin
research of Residual plasma concentrations of amoxicillin
Measured: Day 7
Residual plasma concentrations of administered in high doses amoxicillin
research of Residual plasma concentrations of amoxicillin
Measured: Day 4
Residual plasma concentrations of administered in high doses amoxicillin
research of Residual plasma concentrations of amoxicillin
Measured: Day 1
Secondary outcomes (30)
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Measured: Day 7
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Measured: Day 4
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
research in fresh morning urine sample, examined by microscope then infrared spectroscopy in case of crystalluria
Measured: Day 1
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
plasma concentrations on blood sample
Measured: day 7
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
plasma concentrations on blood sample
Measured: day 4
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
plasma concentrations on blood sample
Measured: day 1
density of urines in g/mL
research in fresh morning urine sample
Measured: Day 7
pH of urines
research in fresh morning urine sample
Measured: Day 7
density of urines in g/mL
research in fresh morning urine sample
Measured: Day 4
pH of urines
research in fresh morning urine sample
Measured: Day 4
density of urines in g/mL
research in fresh morning urine sample
Measured: Day 1
pH of urines
research in fresh morning urine sample
Measured: Day 1
confusional state
Glasgow coma scale
Measured: Day 1
confusional state
Glasgow coma scale
Measured: Day 4
confusional state
Glasgow coma scale
Measured: Day 7
encephalitic signs
focal neurological signs
Measured: Day 1
encephalitic signs
focal neurological signs
Measured: Day 4
encephalitic signs
focal neurological signs
Measured: Day 7
epilepsy
abnormal movement disorders, seizures and status epilepticus
Measured: Day 1
epilepsy
abnormal movement disorders, seizures and status epilepticus
Measured: Day 4
epilepsy
abnormal movement disorders, seizures and status epilepticus
Measured: Day 7
age associated with evolution of amoxicillin plasma concentrations
in years
Measured: Day 0
body mass index associated with evolution of amoxicillin plasma concentrations
weight in kg and height in meters will be combined to report BMI in kg/m^2
Measured: Day 0
renal function at treatment initiation associated with evolution of amoxicillin plasma concentrations
CKD EPI clearance, based on serum creatinine in µmol/L
Measured: Day 0
renal function impairment during treatment
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Measured: Day 1
renal function impairment during treatment
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Measured: Day 4
renal function impairment during treatment
stage of acute kidney injury (based on KDIGO guidelines using variation of serum creatinine in µmol/L compared with baseline, and measure of urine output)
Measured: Day 7
germ involved
full name of bacteria
Measured: Day 0
MIC of germ
MIC in mg/L
Measured: Day 0
site of infection
infected organs
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start4 Dec 2019
- Primary completion19 Dec 2024
- Study completion19 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infection, BacterialStudies of the same condition, open and under way.
- More trials run by University Hospital, Clermont-FerrandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Clermont-Ferrand
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Magali VIDAL, Principal investigator, University Hospital, Clermont-Ferrand
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04070469
- Sponsor's protocol ID
- RBHP 2019 VIDAL (MAX-AMOX)
- Other IDs
- 2019-002824-34, 2019
- Acronym
- MAX-AMOX
- Status last verified
- Aug 2026
- First submitted
- 26 Jul 2019
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Clement M, Anglade F, Gibold L, Martineau D, Dubray C, Ruivard M, Andre M, Tournadre A, Clerfond G, Geoffroy E, Moisset X, Dupuis C, Pereira B, Richard D, Vidal M. Amoxicillin Blood Concentration in High-Dose Intravenous Discontinuous Amoxicillin: Look Beyond Numbers. Max-Amox Study. Clin Ther. 2025 Mar;47(3):212-218. doi: 10.1016/j.clinthera.2024.12.003. Epub 2024 Dec 28.
PubMed 39734108
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Plasma Concentrations of Amoxicillin Administered in High-doses During the First Week of Treatment : Intra- and Inter-individual Variability, Factors Associated With Overdose and Adverse Events
- ClinicalTrials.gov ID
- NCT04070469
- Acronym / sponsor ID
- MAX-AMOX / RBHP 2019 VIDAL (MAX-AMOX)
- Conditions
- Infection, Bacterial
- Keywords
- amoxycillin, drug kinetics, drug toxicity, crystalluria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- University Hospital, Clermont-FerrandUniversity, hospital or other
- Study start
- 4 Dec 2019 (actual)
- Primary completion
- 19 Dec 2024 (actual)
- Study completion
- 19 Dec 2024 (actual)
- First posted
- 28 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Amoxicillin is the most prescribed antibiotic in France. High dose intravenous amoxicillin, (dosage greater than or equal to 150 mg / kg / day or 12 g per day for patients over 80 kg) is used in the treatment, in particular, of infectious streptococcal endocarditis. oral, streptococci gallolyticus and enterococci, infections of the central nervous system with sensitive germs including Streptococcus pneumoniae and Listeria monocytogenes, osteo articular infections. The dose-related adverse effects of this antibiotic are nephrological (crystalluria may lead to acute renal failure) and neurologic. Recently, the number of amoxicillin crystalluria reported to pharmacovigilance centers has increased, having led the National Agency of drug and health products safety (ANSM) to recommend the determination of the residual level of amoxicillin during the first week of treatment of these patients. Nevertheless, there is no precise therapeutic target in patients treated with high dose amoxicillin except in the context of critical care. The authors suggest the interest of a target between 4 and 10 times the minimum inhibitory concentration (MIC) based on in vitro efficacy studies, and retrospective observations of toxicity cases.
Detailed description
Patients will be followed for 8 days. After inclusion, (day of the introduction of high-dose amoxicillin treatment), the residual amoxicillin plasma concentrations will be determined at Day1, Day4 +/- 1 day and Day7 +/- 1 day of the start of treatment. A urine collection will be performed the same day to search for crystalluria and measure the pH and urinary density.
In case of KDIGO (Kidney Disease Improving Global Outcomes) 2 or 3 stage renal failure or neurological signs compatible with overdose, residual amoxicillin and crystalluria and urinary density and urinary pH will be measured during the day of discovery of renal failure.
In the case of KDIGO stage 1 kidney failure, a residual level of amoxicillin and a crystalluria search and the measurement of urinary density and urinary pH will be carried out the following day, when serum creatinine is checked according to usual practices.
At day 7 the clinical and infectious biological evolution of the patient will be collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patient reveiving amoxycillin | Experimental | Drug: Amoxicillinall patient included in this study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Major patient, male or female, who has a bacterial infection requiring high dose intravenous amoxicillin antibiotic therapy (greater than or equal to 150 mg / kg / day with a maximum of 12 grams per day or 12 grams per day for patients over 80 kg), according to ANSM recommendations.
- Able to provide informed consent to participate.
- Covered by a Social Security scheme.
Key exclusion criteria (7 listed)
- Pregnant, breastfeeding, or likely to be pregnant women and in the absence of a negative pregnancy test (blood HCG beta).
- Patients under guardianship, curatorship, deprived of liberties or subject to a safeguard of justice.
- Septic shock justifying treatment with pressurized amines.
- Patient under ventilatory or circulatory support.
- Patients on dialysis at Baseline or with a creatinin clearance less than or equal to 30mL / min
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmoxicillinAlso: amoxicillin treatmentdosage of plasma concentration of amoxicillin | Drug | Patient reveiving amoxycillin |
Primary outcome
Residual plasma concentrations of administered in high doses amoxicillin
Time frame: Day 7
research of Residual plasma concentrations of amoxicillin
Residual plasma concentrations of administered in high doses amoxicillin
Time frame: Day 4
research of Residual plasma concentrations of amoxicillin
Residual plasma concentrations of administered in high doses amoxicillin
Time frame: Day 1
research of Residual plasma concentrations of amoxicillin
30 secondary outcomes
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time frame: Day 7
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time frame: Day 4
search for cystalluria, description of crystals, and infrared spectropscopy to determine crystals composition
Time frame: Day 1
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time frame: day 7
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time frame: day 4
proportion of residual plasma concentrations above 10 minimal inhibitory concentration (MIC)
Time frame: day 1
density of urines in g/mL
Time frame: Day 7
pH of urines
Time frame: Day 7
density of urines in g/mL
Time frame: Day 4
pH of urines
Time frame: Day 4
density of urines in g/mL
Time frame: Day 1
pH of urines
Time frame: Day 1
confusional state
Time frame: Day 1
confusional state
Time frame: Day 4
confusional state
Time frame: Day 7
encephalitic signs
Time frame: Day 1
encephalitic signs
Time frame: Day 4
encephalitic signs
Time frame: Day 7
epilepsy
Time frame: Day 1
epilepsy
Time frame: Day 4
epilepsy
Time frame: Day 7
age associated with evolution of amoxicillin plasma concentrations
Time frame: Day 0
body mass index associated with evolution of amoxicillin plasma concentrations
Time frame: Day 0
renal function at treatment initiation associated with evolution of amoxicillin plasma concentrations
Time frame: Day 0
renal function impairment during treatment
Time frame: Day 1
renal function impairment during treatment
Time frame: Day 4
renal function impairment during treatment
Time frame: Day 7
germ involved
Time frame: Day 0
MIC of germ
Time frame: Day 0
site of infection
Time frame: Day 0
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2026.
- Results publication: PubMed 39734108Clement M, Anglade F, Gibold L, Martineau D, Dubray C, Ruivard M, Andre M, Tournadre A, Clerfond G, Geoffroy E, Moisset X, Dupuis C, Pereira B, Richard D, Vidal M. Amoxicillin Blood Concentration in High-Dose Intravenous Discontinuous Amoxicillin: Look Beyond Numbers. Max-Amox Study. Clin Ther. 2025 Mar;47(3):212-218. doi: 10.1016/j.clinthera.2024.12.003. Epub 2024 Dec 28.
Related trials for Infection, Bacterial
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruitingPhase 2
A Study to Learn About How a New Pneumococcal Vaccine Works in Infants
Pneumococcal Disease
Not yet recruiting
Early Pathophysiology of Hidradenitis Suppurativa and Prediction of the Risk of Progression: a Prospective Cohort
Hidradenitis Suppurativa (HS)
RecruitingPhase 3
A Study to Learn About the Safety of an Expanded Pneumococcal Vaccine in Healthy Infants
Pneumococcal Disease
RecruitingObservational study
Modeling Host-Pathogen Interaction Using Lymphoid Organoids
Staphylococcal Infections
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Magali VIDAL principal investigator
University Hospital, Clermont-Ferrand
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Amoxicillin in people with Infection, Bacterial, run by University Hospital, Clermont-Ferrand at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Residual plasma concentrations of administered in high doses amoxicillin (time frame: Day 7). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04070469, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.